We propose a protocol to "rescue" lymphoma-bearing mice from lethal doses of the anti-cancer drug, Methotrexate (MTX) with N5-methyltetrahydrofolate (N5-CH3-FH4) when the animals are maintained on a methionine-free diet containing DL-homocystine as the only sulfer amino acid. We present evidence from the literature and from our own preliminary experiments which supports the concept that the regimen we propose may provide slelective "rescue" of normal cells in the presence of the L-1210 and L-5178Y neoplastic cells, which are known to be methionine-dependent. We have outlined the studies on whole animals which will be required to refine our protocol so that we may contrast tumor growth in treated and untreated animals. We shall also measure in the tumors the activities of enzymes involved in pathways in sulfur amino acid metabolism, i.e., methionine synthetase, cystathionase, and glycine N-methyltransferase. By exploring the molecular basis for the observed tumor growth in whole animal experiments we shall be expanding current understanding of the comparative biochemistry and sensitivity to MTX of these lymphoma cells. The knowledge obtained by the proposed research could lead to the use of nutritional manipulation as an adjuvant to established cancer chemotherapy programs.